Dynamic Change and Immune Response to Nasopharyngeal Carriage and Acute Otitis Media Pathogens (AOM)

The investigators seek to conduct a prospective, longitudinal study to identify the dynamic changes in nasopharyngeal (NP) colonization patterns and acute otitis media (AOM) etiology involving antibiotic-resistant Streptococcus pneumoniae (Spn) and Haemophilus influenzae (Hflu).

Study Overview

• Status: Active, not recruiting
• Conditions: Acute Otitis Media
• Intervention / Treatment: Procedure: Tympanocentesis; Other: Nasal Phalangeal Swab and Wash; Other: Blood Draw

Detailed Description

The investigator's proposed study design involves 2 cohorts. Cohort 1: Collection of middle ear fluid(MEF), NP samples and blood at onset of AOM from otitis prone children and those who have AOM antibiotic treatment failure since these children more frequently harbor antibiotic resistant strains. Children will then be followed prospectively thereafter, collecting NP samples at pre-determined time points when the children are healthy (see cohort 2) and MEF, NP samples and blood if subsequent AOM infections occur. Cohort 2: Healthy children from whom we will prospectively collect NP samplings and blood at any of 7 pre-determined time points (age 6, 9, 12, 15, 18, 24, and/or 30-36 months old as they occur within the study time-frame) to assess commensal carriage of Spn and Hflu. MEF will be obtained from the participants at any AOM occurring, including the first and any subsequent AOM infection. Concurrently detailed demographic, vaccination, epidemiologic and risk factor data known to influence AOM epidemiology will be collected, providing scientific rigor.

Viral respiratory infections will be another focus during this project. The investigators will characterize dynamic changes in patterns of viral co-infections at onset of AOM including the common respiratory viruses RSV A, B, influenza A, B, parainfluenzae virus type 3, rhinovirus, enterovirus, human metapneumovirus, human bocavirus, adenovirus B, C and SARS-CoV-2. The studies will involve viral identification, evaluation of viral/bacterial (otopathogen) interactions and mucosal and systemic immune responses.

The investigators have identified multiple deficiencies in innate and adaptive immunity among young children who are AOM prone and introduced the term "prolonged neonatal-like immune profile (PNIP) because of striking similarities that resemble neonatal immunity. Another focus of this project will be to expand understanding of the central immune deficiencies of APM prone children using blood samples.

A a serum correlate of protection has been defined to predict the effectiveness of pneumococcal conjugate vaccines using blood samples linked to occurrence of NP colonization and AOM events in recent past work. Blood will be used to continue this work.

• Study Type: Interventional
• Enrollment (Estimated): 320
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Michael Pichichero; Phone Number: 922-5959; Email: michael.pichichero@rochesterregional.org

Study Locations

• United States
  • New York
    • Rochester, New York, United States, 14621
      • Rochester General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 3 years (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male or female subject age 6 to 12 months + 30 days at the time of enrollment when healthy or up to 36 months old + 30 days with an ear infection.
• Subject has received full (3 dose) infant series of PCV.
• Parent/legal guardian must be able and willing to bring subject to all study visits

Exclusion Criteria:

• Any major illness/condition that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in the study.
• Participation in another investigational or interventional trial within the 28-day period before enrollment and during the conduct of the study. Participation in observational studies is permitted.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Healthy Children; Samples taken from nasal swabs, nasal wash, blood draws and in the case of acute otitis media, tympanocentesis	Procedure: Tympanocentesis; When acute otitis media is diagnosed, local anesthetic applied, small hole placed in eardrum, middle ear fluid extracted.; Other Names: Ear Tap; Other: Nasal Phalangeal Swab and Wash; Nasal phalangeal swab used to retrieve sample. Nasal wash used to retrieve sample.; Other Names: Nasal Swab, Nasal Wash; Other: Blood Draw; Venipuncture

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterize which bacterial strains in the NP	Identify the presence of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catharralis in the nasopharynx of children using in vitro culture	30 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterize which bacterial strains are AOM causing pathogens	Identify the presence of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catharralis in the nasopharynx of children using in vitro culture	30 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterize dynamic changes in patterns of viral co-infections at onset of AOM	Identify respiratory viruses present in the nasopharynx at onset of acute otitis media in young children using polymerase chain reaction methods.	30 months
Determine immune responses after NP carriage and AOM infections by the common bacterial respiratory pathogens.	Measure serum and nasopharyngeal antibody levels to common bacterial and viral respiratory pathogens with ELISA and immune cellular responses (B cells, T cells, Antigen Presenting cells using flow cytometry and ELISPOT	30 Months
Determine the serum antibody response that correlates with protection against NP colonization and AOM.	Establish a correlate of protection for pneumococcal serotypes that colonize the nasopharynx and cause acute otitis media in young children using ELISA	30 months

Collaborators and Investigators

• Sponsor: Rochester General Hospital
• Investigators: Principal Investigator: Michael Pichichero, MD, Rochester General Hospital Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: May 24, 2021
• First Submitted That Met QC Criteria: June 24, 2021
• First Posted (Actual): June 30, 2021

Study Record Updates

• Last Update Posted (Actual): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 21, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Otorhinolaryngologic Diseases; Ear Diseases; Otitis; Otitis Media
• Other Study ID Numbers: IRB 2031 A

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No